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Intracavitary Hyperthermic

Perfusion-Chemotherapy (ICHP)
E. Dieter Hager
BioMed-Hospital, Bad Bergzabern, Germany

Workshop Hyperthermia, Cairo, December 21st, 2004

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Methods of Intracavitary Hyperthermic
Perfusion ChTx

• Peritoneal Carcinomatosis
◆ Intraperitoneal (IPHC) • Malignant Ascites
• Pseudomyxoma peritonei
• i.p. disseminated Mesothelioma
• Neoadjuvant, Salvage &
Consolidation Therapy
• Adjuvant (?)
◆ Intrapleural (IPlHC)
• Malignant Pleural Effusion
• Pleural Carcinosis
• Malignant Pleuramesothelioma
◆ Intravesicular (IVHC)
• Recurrent Urothelial Carcinoma
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Rationale for intraperitoneal Treatment
- Pharmacological advantages -
❶❶Spread
Spreadof
of ovarian
ovarian &
& stomach
stomach cancer
cancer occurs
occurs most
most frequently
frequently
into
into the
the peritoneal
peritoneal cavity.
cavity.

❷❷Higher
Higher concentrations
concentrations of
of cytotoxic
cytotoxic drugs
drugswithin
within the
the
peritoneal
peritoneal cavity
cavity following
following i.p.
i.p.drug
drug administration
administration
compared
comparedto to i.v.
i.v. application
application (i.p./plasma
(i.p./plasma concentrations
concentrations
18-1000
18-1000 fold).
fold).

❸❸Increased
Increased exposure
exposure time
time to
to antineoplastic
antineoplastic agents
agents due
due to
to
peritoneal
peritoneal space
space to
to plasma
plasma barrier
barrier

❹❹Reduced
Reduced toxicity
toxicity following
following i.p.
i.p. application
applicationdue
due to
to lower
lower
systemic
systemic concentrations
concentrations of
ofcytotoxic
cytotoxic drugs.
drugs.
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Pharmacological Advantage of I.P.
Administration Compared to Systemic
Drug Molecular Weight AUC Ratio* Synergism with
(i.p./plasma) Hyperthermia
Carboplatin 371 18 potentiating

Cisplatin 300 20 potentiating

Mitomycin C 334 71 potentiating

Methotrexate 455 92 independent

5-Fluorouracil 130 298 independent

Doxorubicin 544 474 additive

Mitoxantrone 517 620 additive

Paclitaxel 854 1,000 additive

* Ratio of antineoplastic agent in the dialysate compared with plasmaedhlevels


ICHS Shenzhen 2004
Peri-/postoperative I.P. Chemotherapy
Preoperative (before surgery)
Perioperative
Intraoperative (during surgery)
Postoperative (early)

S. Fujimoto (Japan) / P.H. Sugarbaker (USA) / F. Gilly (France)/DeSimone (Italy)


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IPHC – Stomach Cancer
- intraoperative -

adjuvant Tx

Peritoneal disseminated stage

Fujimoto et al.: Cancer 1999; 85:529-34

Fujimoto et al.: 1991


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Randomised Controlled Trials with Perioperative
Intraperitoneal Hyperthermic Chemoperfusion

Tumor site Experi-mental Con-trol No. of pts.Relapse after 4-year SR p-value Author
2 yrs

Stomach cancer OP + IPHC 71 9 62% 0.04 Fujimoto 1999


OP 70 18 49%

Stomach cancer OP + IPHC 42 18 64% 0.2 Hamazoe 1994


OP 40 22 53%

Stomach cancer CT + OP + 55 9 52% Crookes 1997


IPHC CT + OP

Abbreviations: RT: radiotherapy; CT: chemotherapy; MW: microwaves; RCT: randomised controlled trial; OT: open-label observational study; CR: complete
response; Rec: recurrence after adjuvant treatment; neoadj.: neoadjuvant; adj.: adjuvant

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Percutaneous Intraperitoneal
Hyperthermic Perfusion-
Chemotherapie of Patients
with Recurrent Peritoneal
Carcinosis from Ovarian
Cancer

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Background

1. After induction CTx more than 80% of pts. with advanced ovarian
cancer (AOC) ultimately relapse from clinical remission.

2. CTx-refractory or -resistant pts. with peritoneal disseminated AOC


respond poorly to systemic therapies of all types.

3. The expected 1-yr OSR of these pts. is < 2%, depending from size of
largest residual tumor mass, time to progression, performance
status, and histological grading.

4. I.p. CTx application increases local concentrations of cytotoxic drugs


and improves RR‘s, but only moderately prolongs survival, if prior
systemic CTx failed.
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Median Overall Survival Time of Patients with
Advanced Cancer of the Ovary (AOC)
- Systemic Chemotherapy -
Chemotherapy FIGO MOS
Stage [months]
A) First-line after surgery
- Single alkylating agents III 12-14
- Platinum-based regimen s III 13-24
- Paclitaxel + cisplatin III, IV 18-38

B) Recurrent and platinum resistant (second-line)


- Topotecan III, IV 10.8
- Etoposide III, IV 10.8
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Patients Surviving 2 Years or Longer After Salvage Abdominal
Irradiation for Disease Found at Second-Look Surgery

Residual Disease

Microscopic Disease < 1 cm > 1 cm

22%* 7%* 0%*


*Young, R. C. et al.: Cancer of the Ovary. In: De Vita V.T. et al.: Cancer: principles and practice in oncology. 4th ed.
(1993)

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Rationale for Hyperthermia (I)

1.1. Hyperthermia
Hyperthermiainduces
inducesapoptosis
apoptosis
(direct
(direct heat-related
heat-relatedcytotoxic/cytostatic
cytotoxic/cytostaticeffects)
effects)

2.2. Synergistic
Synergisticinteractions
interactionsof
ofheat
heatwith
with selected
selected
antineoplastic
antineoplasticagents
agents

3.3. Reduced
Reduced drug
drugresistance
resistance(blood
(bloodperfusion,
perfusion,membrane
membranepermeability,
permeability,
metabolism)
metabolism)

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Rationale for Hyperthermia (II)

1.
1. Immunological
Immunologicaleffects
effectson
on cellular
cellulareffector
effector cells
cellsand
andhumoral
humoral
immune
immuneresponse
response(emigration,
(emigration,migration
migrationand
andactivation)
activation)

2.
2. Induction
Inductionof
of cytokines,
cytokines, chemokines
chemokinesand
andheat
heat shock
shockproteins
proteins

3.
3. Modulation
Modulation of
of cell
celladhesion
adhesionmolecules
molecules

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Objectives

◆◆ Feasibility of IPHC
Feasibility of IPHC
(tolerability,
(tolerability, safty
saftyand
andadverse
adverseevents)
events)

◆◆ Impact on overall median survival time (MST)


Impact on overall median survival time (MST)
&&survival
survival rate
rate(OSR)
(OSR)

◆◆ Effect on Quality of Life (QoL)


Effect on Quality of Life (QoL)

◆◆ Feasibility of long-term therapy


Feasibility of long-term therapy

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Percutaneous Intraperitoneal Hyperthermic
Chemoperfusion
- repeated long-term Tx -

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IPHC-Unit

BioMed-Hospital
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Material and Methods (ascites/flooding)

Verres-Needle

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Material and Methods (perfusion/lavage)
Peritocat 1,5-2,5 mm

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SLH-100 Perfusional Device

◆ Perioperative IPHP
◆ Percutaneous IPHP
◆ Intravesicular ICHP
◆ Endocavitary HT
◆ Isolated Extremity Perfusion
◆ Extracorporal Blood Perfusion

• Easy control of heat exchange


• European certification edh ICHS Shenzhen 2004
Patients and Methods:
Study Design & Eligibility Criteria

Study
 Study Design:
Design:
◆Prospective
◆ Prospective open
open lable,
lable, single-arm
single-arm phase
phase I/II-study
I/II-study

Inclusion
 Inclusion Criteria:
Criteria:
◆Primary
◆ Primary stage
stage III
III or
or IV
IV epithelial
epithelial or
or stromal
stromal ovarian
ovarian
cancer
cancer
◆Advanced
◆ Advanced disseminated
disseminated peritoneal
peritoneal carcinosis
carcinosis
◆Chemotherapy-refractory
◆ Chemotherapy-refractory or or -resistant
-resistant patients
patients
at
at least
least after
after second-line
second-line CTx
CTx

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Patients and Methods:
Eligibility Criteria

 Exclusion Criteria:
◆ No prior platinum- or paclitaxel-based regimen
◆ Extensive abdominal adhesions
◆ Distribution of fluid in compartments < 1.5 l
◆ Multiple bulky tumor masses in the abdomen (> 2 cm),
except of pts. with ascites
◆ Subileus symptomatic (advanced)
◆ History of heavy cardiac arrhythmia
◆ No informed consent

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Methods:
Treatment (IPHC-
Intervention)
◆ IPHC (qwx2-3) 2-4 l physiological saline

◆ IP Chemotherapy (qwx2-3) cisplatin 100 mg


or carboplatin 450 mg
or mitoxantrone 30 mg

◆ Temperatureinput 46-48 °C
intraperitonal (set) 42-43 °C
output 41-43 °C

◆ Perfusion Time 1 h at 42-43 °C

◆ Repetition q1w
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Study Endpoints (IPHC-EOC)

 Primary Endpoint - Overall Survival Time/


Overall Survival Rate

 Secondary Endpoints - Clinical Benefit (QoL)


- Tumor Markers

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Patient Characteristics (I):

◆◆ Total number of patients accrued 38


Total number of patients accrued 38
◆◆ Total number of patients evaluable 36
Total number of patients evaluable 36
◆◆ Median Age (yrs.) [Range] 55
Median Age (yrs.) [Range] 55[22
[22––72]
72]
◆◆ Performance Status (WHO) II==36
Performance Status (WHO) 36%% IIII==53
53%% III
III==11%
11%
◆◆ Sites of Disseminated Metastasesn [%]
Sites of Disseminated Metastasesn [%]
–– Peritoneal
Peritonealcarcinosis
carcinosis36
36[100]
[100]
–– Ascites
Ascites 17
17[47]
[47]
–– Lymph
Lymphnodes
nodes 88[22]
[22]
–– Liver
Liver 55[14]
[14]
–– Abdominal
Abdominalwall
wall 33[8]
[8]
–– Pleura
Pleura 22[6]
[6]
–– Spleen
Spleen 11[3]
[3]

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Patient Characteristics (II):

◆◆Histology
Histology nn (%)
(%)
-- Adenocarcinoma
Adenocarcinoma(serous,
(serous,mucinous,
mucinous,endometriod)
endometriod) 29
29(80)
(80)
--Granulosa-stromal
Granulosa-stromalcell
cell tumor
tumor 22(6)
(6)

--Undifferentiated
Undifferentiatedcarcinoma
carcinoma 22(6)
(6)
--Unclassified
Unclassified 33(8)
(8)

◆◆Grading
Grading nn(%) (%)
--G1
G1== 22(6)
(6) --G3
G3==15
15(42)
(42)
--G2
G2==11
11(30)
(30) --G4
G4== 22(6)
(6)
--unknown
unknown==66(16)
(16)

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Prior Therapies and Tx-free Intervals
◆◆ Prior Chemotherapy i.v. Patients
Prior Chemotherapy i.v. Patients nn(%)
(%) av.
av.No.
No.ofofCourses
Courses
––cyclophosphamide
cyclophosphamide 32
32(89)
(89) 5.8
5.8
––platinum
platinum 34
34(94)
(94) 5.7
5.7
––paclitaxel
paclitaxel 18
18(50)
(50) 4.2
4.2
––others
others 18
18(50)
(50) 6.0
6.0

▲Average

Averagenumber
numberof
ofCTx
CTxcourses
coursesprior
priorto
to1st
1stIPHC
IPHC nn==12.5
12.5

▲Median

Mediantimetimefrom
from1st1stDxDxofofOC
OCto
to1st
1stIPHC-Tx
IPHC-Tx 17.9
17.9mos
mos
(Time to Progression/Resistance)
(Time to Progression/Resistance)

▲Last

Lasttreatment
treatmentfree
freeinterval
intervalpts.
pts.nn(%)
(%) <<44mos
mos 24
24(67)
(67)
(Median
(Median67
67days)
days) 4-12
4-12mos
mos 77(19)
(19)
>>1212mos
mos 55(14)
(14)
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IPHC – Treatment (EOC)

◆Total
◆ Total number
number of
of IPHC-treatments
IPHC-treatments 168
168
◆Follow-up
◆ Follow-up time
time 3.3
3.3 yrs.
yrs.
◆Follow-up
◆ Follow-up rate
rate 94
94 % %
◆Number
◆ Number of
of pts.
pts. still
still alive
alive at
at time
time of
of 77 (censored)
(censored)
assessment
assessment

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Kaplan-Meier Curve for Survival from 1st IPHC-
Treatment of Patients with Ovarian Cancer
(all Patients n = 36)
Survival Function IPHT
1,0

,8

,6

,4
cum. survival

,2

survival function

0,0 censored
0 1 2 3 4 5 6 7

[Survival from start of IPHT in years]

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Survival from 1st Dx of OC vs. 1st IPHC-Tx
(Kaplan-Meier Estimation)

Survival Function IPHT


1,0

,8

,6

,4

2,00 from IPHT


cum. survival

,2
2,00-censored

1,00 from dx

0,0 1,00-censored
0 2 4 6 8

[overall survival from dx vs. survival from IPHT in years]

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Median Survival from 1st IPHC
Ascites vs. non-Ascites (Kaplan-Meier Estimation)

Survival Function IPHT


1,0

,8

,6

,4
P=0.4 ASCITES
cum. survival

yeas 1

,2
1-censored

no 0

0,0 0-censored
0 1 2 3 4 5 6 7

[Survival from start of IPHT in years]

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Results: Median Survival Time (IPHC-OC)
(Kaplan-Meier-Estimation)
◆ From 1st IPHC-Treatment Median
(months)
Patients with Ascites ( n = 17) 15 ± 2
[range] [2 – 84+]

Patients without Ascites (n = 19) 24 ± 2


[range] [4 – 55+]
all Patients (n = 36) 19 ± 4
[range] [2 – 84+]

✦ From 1st diagnosis of AOC:


all Patients (n = 36) 49 ± 8
[range] [8 – 88+]

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Results 2: Survival Rates from 1st IPHC
(Ascites vs. non-Ascites)

1-year
1-year 2-year
2-year 3-year
3-year 4-year
4-year 5-year
5-year
%% %
% %
% %
% %%
From
From1st
1stIPHC-Tx:
IPHC-Tx:
Pts.
Pts.with
withAscites
Ascites 63
63±±12
12 31
31±±12
12 25
25±±1111 17
17±±1010 17
17±±10
10
Pts.
Pts.without
withoutAscites
Ascites 68
68±±11 45
45±±11
11 34
34 ±±11
11 15
15±±99 15
15±±99
all
allPatients
Patients 65
65±±88 39
39±± 88 30
30±±88 16
16±±77 16
16±±77

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Adverse Events of IPHC in % of Total Tx
(n = 168)
WHO-Grade
WHO-Grade 00 11 22 33 44
◆◆ Gastrointestinal
Gastrointestinal
––Nausea/Vomiting
Nausea/Vomiting 30
30 29
29 27
27 14
14 --
––Diarrhoe
Diarrhoe 97
97 22 11 -- --
––SGOT/SGPT
SGOT/SGPT 100
100 -- -- -- --
◆◆ Blood
Blood
––Leucocytes
Leucocytes 96
96 22 22 -- --
––Platelets
Platelets 99
99 -- -- -- 11
––Haemogobulin
Haemogobulin 92
92 55 33 -- --
◆◆ Renal
Renal
--Kreatinin
Kreatinin 92
92 66 22
◆◆ Fever 97 33 -- -- --
Fever 97 edh ICHS Shenzhen 2004
Adverse Events of IPHC in % of Total Tx:
- Treatment Specific -

◆Peritoneal
◆ Peritoneal irritations
irritations 5%*
5%*
◆Subileus
◆ Subileus symptomatic
symptomatic 2%*
2%*
◆Local
◆ Local reactions
reactions (vaccination
(vaccinationmetastases)
metastases) 2/36
2/36 pts.
pts.
◆Bowel
◆ Bowel obstruction
obstruction or
or perforation
perforation 0%*
0%*
◆Catheter
◆ Catheter related
related infections
infections 0%*
0%*
**%
%ofoftreatments
treatments(n
(n==168)
168)

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IPHC
- Contraindications -

◆◆ Extensive GI-adhesions
Extensive GI-adhesions

◆◆ Large tumor volume


Large tumor volume

◆◆ Fistulae
Fistulae

◆◆ Subileus (advanced stage)


Subileus (advanced stage)

◆◆ Peritonitis
Peritonitis

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Summary

1.
1. IPHC
IPHC is
is technically
technically feasible,
feasible, safe
safe and
and well
well
tolerated
tolerated
2. High
2. High response
response ratesrates are
are obtained
obtained in in pts.
pts.
with
with recurrent,
recurrent, chemotherapy
chemotherapy refractory
refractory or
or
resistant,
resistant, peritoneal
peritoneal disseminated
disseminated AOC AOC
3. Reversal
3. Reversal ofof drug
drug resistance
resistance isis possible
possible
4. Increase
4. Increase inin overall
overall survival
survival is
is substantial
substantial
5. Quality
5. Quality ofof life
life can
can be
be improved
improved
6. Adverse
6. Adverse drug
drug reactions
reactions are
are less
less severe
severe
compared
compared to to systemic
systemic chemotherapy
chemotherapy
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Conclusions
1. Optimal
1. Optimal dose
dose and
and schedule
schedule has
has still
still to
to be
be defined
defined
2. IPHC
2. IPHC could
could be
be recommended
recommended as
as „palliative“
„palliative“ therapy
therapy
for
for pts.
pts. with
with CTx-refractory
CTx-refractory or or –resistent
–resistent peritoneal
peritoneal
carcinomatosis
carcinomatosis or or sarcomatosis
sarcomatosis from from AOC
AOC
3. IPHC will be 1 Tx
IPHC will be 1 Tx for
for elimination
elimination of of ascites
oo
3. ascites
4. Could
4. Could be
be ofof advantage
advantage in in aa „salvage“
„salvage“ therapy
therapy
setting.
setting. Phase
Phase IIII studies
studies should
should be be performed.
performed.
5. IPHC
5. IPHC may
may be be possible
possible as as „consolidation“
„consolidation“ therapy
therapy of
of
stage
stage III/IV
III/IV pts.
pts. with
with PRPR or
or MR
MR toto standard
standard induction
induction
therapy.
therapy. RCTRCT should
should bebe performed.
performed.

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Intravesicular Hyperthermic
Perfusion Chemotherapy (IVHC)

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Intravesicular Perfusion Hyperthermia with Catheter

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IVHC with Microwaves

Radiativ (intravesicular microwave antennae, f.e. SYNERGO®)

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IVHC of Pts. with Superficial Bladder Cancer with
intravesicular MW-Antennae (915 MHz) (neoadjuvant)

Colombo, R. et al.: J. Urol. 1996;155:1227-1252


Colombo, R. et al.: Eur. Urol. 1999;35 Suppl. 2
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Advanced Bladder Cancer

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Bladder Cancer – IVHC

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Bladder Cancer – PR/SD

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Carcinoma of the Bladder:
Study Design & Eligibility Criteria

Study Design:
◆ Prospective, Open Lable, Single-Arm Phase II-Study

Inclusion Criteria:
◆ Recurrent and/or Progressive* Bladder Carcinoma
◆ rcTis,a,1/2 rcN0 rcM0, Rx, rG 2-3
◆ Prior TUR-B and Chemo-/Immunotherapy
◆ Indication for Cystectomy**
◆ Informed Consent
* infiltration (T-stage), dedifferentiation (G-Stage), Recurrence rate
**pt. refused/delayed surgery
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Cancer of the Bladder- IVHP
Study-Endpoints

Primary Endpoints - Recurrence rate


- Recurrence free survival

Secondary Endpoints - Prevention of cystectomy


- Clinical benefit (QoL)
- Downstaging (T&G)

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Statistics

◆ Recurrent free survival Kaplan-Meier-Estimation

◆ Recurrence rates descriptive

◆ Intention-to-treat analysis

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Patient Characteristics I

◆ Number of Patients (male/female) 10 (8/2)


◆ Median Age (yr) (Range) 61 (50 - 68)
◆ Karnofsky Index 100 % (n = 4) 90 % (n = 6)

◆ Stage n
rc T1 8
r T2 2
◆ Grading
r G2 7
r G3 3
◆ Histology
urothelium carcinoma 9
unknown 1 edh 09/01
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Patient Characteristics II
Recurrence before IVHP

■ Av. No. of total Recurrences/pt. (range) 6.3 (1 - 12)

■ total Recurrence Rate (RR*) (range) 15.5 (7 - 28.7)

number of positive cystoscopies


* RR = -----------------------------------------
months reexaminations

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Treatment and Statistics

◆ Total No. of IVHP- Tx 56

◆ Mean No. of IVHP-Tx/Pt. (Range) 4.9 (1-13)

◆ Mean Follow-up Time* 74 months

◆ Follow-up Rate 100 %

◆ No. Pts. Alive at Time of Estimation 9

* since last IVHP


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Prior Chemotherapy and IVHP

◆ Prior Chemotherapy* Pts. n av. # of Courses

Mitomycin 5 4
Doxorubicin 2 10

▲ Mean Time from 1st dx to 1st IVHP-Tx: 2.8 yrs (0.3 - 7.6)

*intravesical

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Cancer of the Bladder
IVHP - Intervention

◆ Intravesical Perfusion Volume 100-300 ml saline dialysate

◆ Intravesical Chemotherapy Mitomycin (MMC) 10 mg

◆ Intravesical Temperature Input T 46-48°C


Intravesical T 42-43°C
Output T 41-42°C

◆ Perfusion Time at 42-43o C 1h

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Results: Case reports of pts. with
Reccurent Bladder Cancer
K.E. * 03.12.40

2
1,8
1,8
1,6
Relapses/Year

1,4
1,2
1
0,8
0,6
0,4
0,2
0
0
6/3,3 Years 0/3,5 Years

Prae/Post IVHT(n = 1 treatment) U.G. *29.01.26


1,4
1,25
1,2

1
Relapses/Year

0,8

0,6

0,4

0,2

0
0
9/7,2 Years 0/3,9 Years

Prae/Post IVHT (n = 4 treatments)


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Case Report B.M.

Bladde r Cance r (case re port B.M .) - Re curre nce s

6 MMC, KLH

5
IVHC

4
No Foci

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Results: Interavesicular Hyperthermic Perfusions-Chemo-
therapie (IVHC) in Patients with recurrent Bladder Cancer

IVHT - Blasenkarzinom
4,00

3,50

3,00

2,50
Rezidivrate/Jahr

2,00

1,50

1,00 edh ICHS Shenzhen 2004


Results: Recurrence Rate of Bladder Cancer
after IVHC - Kaplan-Meier-Estimation -

p < 0.01

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Adverse Effects of IVHP in % of Total Treatments (n = 39)

WHO-Grade 0 1 2 3 4

◆ Pain 100 - - - -

◆ Infection/Fever 100 - - - -

◆ Cystitis 86 14 - - -

◆ Uremia 100 - - - -

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Summary & Conclusions

◆ IVHP combined with CTx seems to be a feasible, safe and


promising approach for the treatment of recurrent bladder
cancer

◆ Chemotherapy-resistance may be reduced by heat

◆ Recurrence rate/recurrence-free suvival decreased


significantly

◆ Bladder-sparing seems to be possible by IVHC

◆ The efficacy should be demonstrated in larger randomized


trials
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Conclusions:
Indications for IVHP-CTx

➨ Neoadjuvant therapy (downstaging)

➨ Adjuvant therapy (relapse prophylaxis after TUR-B)

➨ Bladder-sparingtherapy for superficial and invasive,


recurrent bladder cancer

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Recurrence Rate of Bladder Cancer after IVHC

Bladder Cancer - IVHT


1.0

0.8
GROUP
1
Probability

0.6 2
3

0.4

0.2

0.0
0 500 1000 1500 2000 2500
Time: to recurrence/recurrence-IVHT
edh ICHS Shenzhen 2004
Randomised controlled and observational trials with
intravesicular hyperthermic perfusion chemotherapy

Tumor site Experi-mental Con-trol No. of pts. OR [%] OR [%] with Survival Re- Ref.
Control HT benefit marks

Bladder, neoadj. MW + CT CT 52 CR: 22 CR: 66 Yes RCT 53

Bladder, adj. MW + CT CT 58 Rec: 64 Rec: 15 Yes RCT 54

Bladder, recurrent hyperthermic 10 90 Yes OT 55


perfusion + CT

Abbreviations: RT: radiotherapy; CT: chemotherapy; MW: microwaves; RCT: randomised controlled trial; OT: open-label observational study; CR: complete
response; Rec: recurrence after adjuvant treatment; neoadj.: neoadjuvant; adj.: adjuvant

edh ICHS Shenzhen 2004


Summary & Conclusion
◆ Long-term, percutaneous or intravesicular
hyperthermic perfusion-chemotherapy is one
of the most powerful new treatments in
oncology

◆ It is feaseable and has minimal side effects


compared to standard chemotherapy

◆ It can be repeated oftenly (> 30 Tx)


edh ICHS Shenzhen 2004